Magnetic targeting enhances retrograde cell retention in a rat model of myocardial infarction

Abstract

IntroductionRetrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.MethodsRat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1 × 106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained.ResultsThe flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved.ConclusionsThese results suggest that magnetic targeting offers new perspectives for retrograde coronary venous delivery to enhance cell retention and subsequent functional benefit in heart diseases.

Magnetic resonance hypointensive signal primarily originates from extracellular iron particles in the long-term tracking of mesenchymal stem cells transplanted in the infarcted myocardium

“…The quantity and duration of SPIO deposition in the myocardium is far beyond that observed in previous intravenous studies, [41][42][43] in which SPIO was administered systemically and proved to be a safe and efficient MR contrast agent. The situation is even worse in the context of SPIO-based magnetic targeting therapy, which was recently introduced for treating cardiovascular diseases, [44][45][46][47] in which more SPIO, alongside therapeutic drugs/ cells, will be homing to the target area of the heart. Fourth, as shown in this study, the iron particles were almost all located in fibrous tissue, and no iron deposits were observed in the normal myocardium in the peri-infarct region at 6 months after cell injection.…”

Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA-conjugated nanoparticles

“…Provided therapeutic agents (eg, exogenously administered cells, growth factors, peptides, or small molecule compounds) could be connected with CREKA effectively and efficiently, the fibrin-targeting system could be capable of localizing systemically delivered cells/drugs to the injured heart, enhancing their efficacy and reducing their dosing. 33,48 In addition, fibrin is the common provisionally pathological matrix after …”

Materials for cardiac tissue engineering

“…Magnetic targeting was used to direct cells with regenerative potential to damaged areas, and to enhance cell retention and engraftment [64][65][66]. The incorporation of iron oxide nanoparticles into microcapsules comprising MSCs, agarose, ECM proteins, collagen, and fibrin highly increases cell survival and retention [67].…”